Is AGAP6 p.Pro682Arg (c.2045C>G) pathogenic?

AGAP6 p.Pro682Arg (c.2045C>G) is classified Uncertain significance in AGAP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: likely benign (0.146); Very rare (popmax 0.00224%, eas).

How common is AGAP6 p.Pro682Arg (c.2045C>G) in the general population?

AGAP6 p.Pro682Arg (c.2045C>G) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about AGAP6 p.Pro682Arg (c.2045C>G)?

AlphaMissense predicts likely benign (score 0.146) — an in-silico prediction, not a clinical call.

AGAP6 p.Pro682Arg

c.2045C>G · rs1554865654 · VCV2517368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.146	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -12.74	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	phastCons 0.95
Regional constraint	o/e 0.11	constrained · MANE · 132 bp · p 8.1e-13 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P659R vs ClinVar P682R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,734 alleles

Overall 6.88e-05% 1/1,453,822 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AGAP6
Protein: p.Pro682Arg
Coding: c.2045C>G
MANE Select: NM_001077665
dbSNP: rs1554865654
Type: single nucleotide variant
Location: chr10:50010170 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.73

Full AGAP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP6 p.Ala105Thr Uncertain significance ★ ⚠ same type
AGAP6 p.Ala109Thr Uncertain significance ★ ⚠ same type
AGAP6 p.Ala135Val Uncertain significance ★ ⚠ same type
AGAP6 p.Ala180Gly Uncertain significance ★ ⚠ same type
AGAP6 p.Ala425Thr Uncertain significance ★ ⚠ same type
AGAP6 p.Ala433Val Uncertain significance ★ ⚠ same type
AGAP6 p.Ala43Ser Uncertain significance ★ ⚠ same type
AGAP6 p.Ala444Pro Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/agap6-p-pro682arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown